Vestibular (inner ear) disorders can cause dizziness, vertigo, imbalance, hearing changes, nausea, fatigue, anxiety, difficulty concentrating, and other symptoms, with potentially devastating effects on a person's day-to-day functioning, ability to work, relationships with family and friends, and quality of life.
Anti-histaminergic compounds are widely used as treatments against vestibular disorders, like vertigos. Histaminergic agonists and antagonists act on the vestibular system both peripherally and centrally, and could interfere with the recovery process after peripheral vestibular lesion (Lacour and Sterkers, 2001). Histamine receptor family comprises four subtypes: H1 and H2 receptor discovered in 1966, H3 receptor discovered in 1983 and H4 receptor identified in 2000. The H4 receptor was identified on the basis of its homology with the H3 receptor (31% at protein level and 54% within the transmembrane membrane). Over the four histamine receptors (HR1 to HR4) HR3 appeared to regulate the vestibular inputs (Chavez 2005). In the field of the histaminergic treatment of vertigo, betahistine (BH) is one of the broad range of antivertiginous compound. The facilitator action of BH has been described in central vestibular compensation (Lacour and Sterkers, 2001; Tighilet et al. 2005), but its effects on peripheral vestibular receptors has only been reported in lower vertebrates (Housley et al. 1988; Tomoda et al. 1997; Botta et al. 1998; Soto et al. 2001; Chavez et al. 2005). BH has been reported to present a complex function as an agonist of H1 histaminic receptor, and as an antagonist of the H3 receptor (Arrang et al. 1985). In the peripheral vestibular receptors isolated from axolotl, BH inhibits the afferent discharge with an IC50 of 800 μM and a maximum effect around 10 mM (Chavez 2005). These studies concluded that histamine H3 receptor was the main target of BH (Van Cauwenberge and De Moor 1997; Soto 2001; Chavez 2005). A recent study realized in cultured rat vestibular neurons, maintained 7 days in vitro, reveals that the application of BH induced a reversible depolarisation of the neuron's membrane and inhibited the evoked discharge without affecting the intrinsic properties of the action potentials.
However, no investigation on Histamine H4 receptor has been made on vestibular disorders.